November 2012

November 26, 2012

In the
latest edition of JCB, Samejima et
al. reveal how the kinesin motor KIF4 helps compact mitotic chromosomes into
their characteristic X shape. KIF4 appears to work with condensin to compact
chromosomes laterally, while the enzyme topoisomerase IIalpha controls an opposing pathway that
shortens chromosome arms. The authors describe the contributions of each
protein in this week’s In Focus, and explain why they think addition
chromosome-shaping proteins remain to be identified.

Lee
et al. reveal how a protein linked to the peripheral neuropathy
Charcot-Marie-Tooth disease (CMT) regulates the endosomal trafficking and
activity of signaling receptors. Charcot-Marie-Tooth type 1C is cause by
mutations in an early endosomal protein called SIMPLE, which, Lee et al. show,
works with ESCRT complex proteins to direct certain receptor tyrosine kinases
to the lysosomes for degradation. Cells expressing mutant versions of SIMPLE
fail to degrade these receptors, leading to prolonged downstream signaling
activity. More here.

Drawnel
et al. describe how a calcium channel and a microRNA regulate each other to
promote pathological remodeling of heart muscle. Various stresses cause
cardiomyocytes to grow larger, a response driven by the upregulation of the
inositol triphosphate receptor IP3RII, which releases calcium from
intracellular stores. Drawnel et al. demonstrate the existence of a positive
feedback loop, in which the calcium released by IP3RII downregulates
a microRNA, miR-133a, that normally represses IP3RII expression. IP3RII
therefore promotes its own expression to drive cardiac hypertrophy. You can
read more here.

And Huang
et al. investigate cytokinetic rings are assembled in S. pombe. Fission
yeast are thought to construct their cytokinetic actomyosin rings from actin
filaments nucleated at myosin-containing nodes around the cell equator. Using
an improved actin-binding probe, Huang et al. find that actin cables are
nucleated all over the cortex of mitotic fission yeast and are transported to
the division site for incorporation into the contractile ring. You can read
more in this summary or listen to senior author Mohan Balasubramanian discuss
his lab’s results in this month’sbiosights video podcast, which you can watch
below or subscribe to in iTunes. And, if you’d like to discuss the implications
of Huang et al.’s study with your colleagues, you can download a “Journal Club
Pack” – including a pdf of the paper and a PowerPoint file of their figures.

November 12, 2012

In
today’s new issue, Reymond et al. describe how the Rho family GTPase Cdc42
helps metastasizing cancer cells move out of the bloodstream to colonize new
tissues. The researchers find that Cdc42 promotes the expression of the
adhesion receptor β1-integrin, which allows cancer cells to attach to
endothelial cells and their underlying extracellular matrix, facilitating their
migration across the endothelial barrier. As explained in this week’s In Focus,
inhibiting this process by transiently depleting Cdc42 is sufficient to reduce
the formation of metastases in vivo.

TerBush
and Osteryoung examine the different contributions of two cytoskeletal proteins
to chloroplast division. Together, the tubulin-like GTPases FtsZ1 and FtsZ2
form a Z-ring at the equator of chloroplasts that helps the organelle divide in
two. By expressing the proteins in fission yeast, TerBush and Osteryoung
suggest that FtsZ2 mainly dictates the Z-ring’s shape, whereas FtsZ1 determines
the structure’s dynamics. More here. And staying with organelle division, Bui
et al. describe how the dynamin-related protein Dnm1 is recruited to the outer
membrane of yeast mitochondria in order to drive mitochondrial fission. You can
learn more in this summary.

Li
et al. reveal that the ARL13B GTPase, which is mutated in the human ciliopathy
Joubert Syndrome, must be conjugated to the small, ubiquitin-like modifier SUMO
to promote the targeting of sensory receptors into the primary cilium. Cells
expressing a non-SUMOylatable version of the GTPase still form cilia, but
several receptors fail to localize to the ciliary membrane, disrupting various
signaling pathways. Senior author Jinghua Hu explains here how this might
explain some of the symptoms suffered by Joubert syndrome patients.

And
Raab et al. describe the distinct contributions of myosin IIA and myosin IIB to
durotaxis, the phenomenon in which cells migrate from softer to stiffer
matrices. Senior author Dennis Discher discusses his lab’s results in this
month’sbiobytes podcast, where you can also hear Ivan Nabi describe his recent
study (Joshi et al.) revealing that caveolin-1 acts as mechanotransducer to
increase the assembly of plasma membrane caveolae to help cells cope with
mechanical stress. You can listen below, or subscribe in iTunes.

There
are lots of other interesting papers in today’s new issue – you can find them
all on our table of contents here – but, finally for today, I’ll point you in
the direction of the latest in our series of features on Cell Biology and
Biomedicine. Oliver Hantschel and Giulio Superti-Furga describe how basic cell
biological research is now one of the key drivers for therapeutic innovations,
Larry Goldstein discusses the therapeutic potential of pluripotent stem cells,
and Alfred Goldberg details the development of proteasomal inhibitors as
anti-cancer agents.

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